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Update on Acute Severe Respiratory Infections: 2nd Edition

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A Special Issue of Journal of Clinical Medicine (ISSN 2077-0383) belonging to the section "Respiratory Medicine".

Deadline for manuscript submissions: 25 March 2027 | Viewed by 6321

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Prof. Dr. Jean-Francois Timsit

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1. Medical and Infectious Diseases ICU, APHP Bichat Hospital F, 75018 Paris, France
2. UMR 1137, IAME, Université Paris Cité, 75018 Paris, France
Interests: severe infections; pneumonia; catheter related infections; sepsis; survival models; high quality databases; ARDS; nosocomial; multiresistant bacteria; outcome
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Dear Colleagues,

We sincerely invite you to contribute to this Special Issue, “Update on Acute Severe Respiratory Infections: 2nd Edition”. (The first edition is available at: Special Issue “Update on Acute Severe Respiratory Infections”, https://www.mdpi.com/journal/jcm/special_issues/9042H9KMCN). This Special Issue combines original research and review papers, with a focus on recent advances in the field of respiratory infections.

Acute severe respiratory infections (ASRI) represent a critical challenge in clinical medicine, encompassing a spectrum of life-threatening conditions such as severe pneumonia, acute respiratory distress syndrome (ARDS), and exacerbations of chronic lung disease. These infections are often caused by viral (e.g., influenza virus, SARS-CoV-2, respiratory syncytial virus), bacterial, or fungal pathogens and require rapid diagnosis, targeted therapy, and advanced supportive care to reduce their high morbidity and mortality. Recent advances in diagnostic techniques, immunomodulatory therapies, and lung-protective ventilation strategies have transformed the management of ASRI. However, emerging pathogens, antimicrobial resistance, and variable host immune responses continue to complicate treatment paradigms.

This Special Issue focuses on cutting-edge research and evidence-based updates in the epidemiology, pathophysiology, and multidisciplinary management of ASRI, with the goal of optimizing treatment outcomes in both immunocompetent and vulnerable populations and of providing the latest information in this field for critical care physicians and other clinicians involved in the care of patients with pneumonia.

Prof. Dr. Jean-Francois Timsit
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

acute severe respiratory infection (ASRI)
acute respiratory distress syndrome (ARDS)
severe pneumonia
sepsis
ICU
viral respiratory infection
COVID-19
bacterial co-infection
diagnostic technology
treatment strategy
mechanical ventilation
extracorporeal membrane oxygenation (ECMO)
antibiotics
non-antibiotics
pulmonary rehabilitation

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Update on Acute Severe Respiratory Infections in Journal of Clinical Medicine (8 articles)

Published Papers (6 papers)

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Research

18 pages, 1250 KB

Open AccessArticle

Neutrophil-to-Lymphocyte Ratio, Systemic Immune-Inflammation Index, and HALP Score as Predictors of Mortality in Acute Respiratory Distress Syndrome

by Anwar A. Sayed, Layan A. Alrehaili, Alhanouf O. Alsuhaymi, Ethar H. Alnuzha, Ghaida T. Alsaedi, Raghad M. Alsharif, Shaden H. Alsaedi, Shatha S. Althubyani, Taif A. Alahmadi and Wurayf F. Alharbi

J. Clin. Med. 2026, 15(11), 4344; https://doi.org/10.3390/jcm15114344 - 4 Jun 2026

Cited by 1 | Viewed by 881

Abstract

Background: Acute respiratory distress syndrome (ARDS) remains one of the most serious causes of respiratory failure and mortality in critically ill patients. Although the Berlin Definition provides a standardized framework for diagnosis, it offers limited predictive value for clinical outcomes. In this context, there is growing interest in the use of routinely available hematological markers as practical tools for early risk stratification. This study aimed to examine the association between hematological parameters and mortality in patients with ARDS, with particular emphasis on complete blood count-derived inflammatory indices. Methods: This multicenter retrospective cohort study included 404 adult patients with a confirmed diagnosis of ARDS who were admitted to intensive care units in Saudi Arabia. Demographic, clinical, and laboratory data were collected from electronic medical records. In addition to standard hematological parameters, the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and hemoglobin–albumin–lymphocyte–platelet (HALP) score were calculated from admission laboratory findings. Comparisons between survivors and non-survivors were performed using non-parametric statistical tests, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic performance of these indices for in-hospital mortality. Results: Of the 404 included patients, 295 survived, and 109 died during hospitalization. Non-survivors demonstrated significantly higher white blood cell and neutrophil counts, alongside significantly lower lymphocyte, eosinophil, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and albumin levels. The derived inflammatory indices further demonstrated clear differences between outcome groups, as NLR and SII were significantly higher in non-survivors, whereas HALP scores were significantly lower. In ROC analysis, NLR showed the strongest discriminatory ability for mortality (AUC = 0.80, 95% CI 0.74–0.85), followed by SII (AUC = 0.76, 95% CI 0.71–0.81) and HALP (AUC = 0.76, 95% CI 0.70–0.81). The optimal cutoff values were 4.26 for NLR, 958 for SII, and 2.15 for HALP. No significant correlations were identified between age and any of the three indices. Upon applying multivariable regression analysis, only NLR maintained its prognostic ability for ARDS-related mortality. Conclusions: Routine hematological parameters, together with derived inflammatory and nutritional indices, were significantly associated with mortality in patients with ARDS. Among the evaluated markers, NLR demonstrated the strongest prognostic performance, both in univariate and multivariate analysis, followed by SII and HALP. As these indices are derived from inexpensive, readily available laboratory tests, they may offer practical value for early risk stratification and clinical decision-making, particularly in resource-limited settings. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections: 2nd Edition)

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16 pages, 3986 KB

Open AccessArticle

A Retrospective Unicenter Study of Clinical and Inflammatory Features in Hospitalized Adults with Respiratory Syncytial Virus Infection Across Two Epidemic Waves in Catalonia, Spain

by Simona Iftimie, Julia Fambuena-González, Andrea Jiménez-Franco, Joaquín Fernández-López, Eva María Declara-Declara, Ana Felisa López-Azcona, Xavier Gabaldó-Barrios, Jordi Camps and Antoni Castro

J. Clin. Med. 2026, 15(11), 4184; https://doi.org/10.3390/jcm15114184 - 28 May 2026

Viewed by 580

Abstract

Background: Respiratory syncytial virus (RSV) is a serious disease in older adults and is associated with various comorbidities; however, comparative data across epidemic waves, both clinically and in terms of inflammatory profiles and their diagnostic and prognostic utility, remain limited. Methods: We conducted a retrospective study of adults hospitalized with RSV infection across two epidemic waves (2022–2023 and 2024–2025). Data on clinical characteristics, comorbidities, severity scores, and outcomes were collected, and serum interleukin-6 (IL-6), C-reactive protein (CRP), and hematological parameters were analyzed and compared with those in healthy controls. Results: A total of 152 patients were included in this study (81 in wave 1 and 71 in wave 2). Patients in wave 2 were older and had a higher burden of comorbidities, although ICU admission and in-hospital mortality were similar across waves. RSV induced a consistent systemic inflammatory response in both waves, characterized by elevated IL-6 and CRP levels, neutrophilia, lymphopenia, and increased neutrophil-to-lymphocyte ratios, with no relevant inter-wave differences. All biomarkers demonstrated good diagnostic performance. The neutrophil-to-lymphocyte ratio showed the highest accuracy, while IL-6 exhibited high rule-in capacity. However, none of the evaluated biomarkers were associated with disease severity or mortality. Conclusions: RSV infection in older adults is associated with a similar inflammatory profile across waves. Although biomarkers showed strong diagnostic utility, they did not show any significant prognostic discrimination in this cohort. We suggest that disease severity is primarily associated with host-related factors, particularly comorbidities, rather than with differences in the inflammatory response, highlighting the need for improved preventive and risk-stratification strategies in this population. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections: 2nd Edition)

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16 pages, 746 KB

Open AccessFeature PaperArticle

Lung Ultrasound Abnormalities and LUS Score After COVID-19 Pneumonia: Determinants and Associations with Dyspnoea in a Prospective Cohort

by Francisco Navarro-Romero, Cristina Asencio-Méndez, Francisco Rivas-Ruiz, Blanca Sánchez-Mesa, María Dolores Martín-Escalante and Julián Olalla-Sierra

J. Clin. Med. 2026, 15(9), 3438; https://doi.org/10.3390/jcm15093438 - 30 Apr 2026

Viewed by 557

Abstract

Background/Objectives: The clinical determinants and functional relevance of persistent lung ultrasound (LUS) abnormalities after COVID-19 pneumonia remain poorly characterized. We aimed to identify determinants of qualitative LUS abnormalities and global lung involvement assessed by the LUS score, and to evaluate their association with persistent dyspnoea. Methods: We conducted a prospective observational study that included 261 patients who were hospitalized for COVID-19 pneumonia and were assessed 1–6 months after discharge. A standardized 14-zone LUS protocol was used to assess qualitative abnormalities (pleural line irregularity, ≥3 B-lines, and subpleural consolidations) and to calculate the LUS score. Associations with clinical variables, including dyspnoea assessed by the modified Medical Research Council (mMRC) scale, were analyzed using multivariable logistic regression. Results: The severity of the acute pneumonia episode emerged as the strongest determinant of qualitative LUS abnormalities and elevated LUS score (>6). Increasing age was independently associated with ultrasound findings. Persistent dyspnoea (mMRC ≥ 1) was associated with all qualitative abnormalities and with a higher prevalence of elevated LUS score (56.6% vs. 22.1%; p < 0.001). A graded association was observed between dyspnoea severity and both qualitative findings and LUS score. An increase in dyspnoea from baseline (ΔmMRC ≥ 1) remained independently associated with an elevated LUS score. Conclusions: Persistent LUS abnormalities are strongly associated with the severity of the acute episode. The LUS score provides a robust, clinically meaningful measure of residual lung involvement and shows a stronger association with persistent dyspnoea than qualitative findings, supporting its role in follow-up and risk stratification. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections: 2nd Edition)

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16 pages, 763 KB

Open AccessArticle

New Simplified White Blood Cells Score Improves Mortality Prediction in Severe COVID-19 Patients

by Kamil Paryż, Arkadiusz Lubas, Mateusz Gutowski, Bartosz Rustecki, Andrzej Michałowski and Jakub Klimkiewicz

J. Clin. Med. 2026, 15(7), 2590; https://doi.org/10.3390/jcm15072590 - 28 Mar 2026

Viewed by 934

Abstract

Background: An unfavorable course of SARS-CoV-2 infection can lead to significant morbidity and mortality. The study aimed to develop a simple, accessible, and reliable tool to anticipate the poor results among COVID-19 pneumonia patients. Methods: This retrospective cohort study involves 306 individuals with severe COVID-19 pneumonia enrolled between March 2021 and June 2021. Each patient had confirmed SARS-CoV-2 infection and required oxygen therapy. Differential blood count and serum CRP were taken on admission day. Medical data were collected from the hospital’s information system. Results: Of 306 patients (133 females, 173 males, aged 66.3 ± 15.2 years), 105 (34.3%) died. Counts of neutrophils, lymphocytes, and eosinophils differed significantly between survivors and deceased (p < 0.001; p = 0.002; p = 0.009, respectively) and had substantially differentiating properties in ROC analysis. Built with the counts of neutrophils, lymphocytes, and eosinophils, the White Blood Cell Score (WBCS) was developed. WBCS robustly predicted mortality (OR = 2.821; CI: 2.037–3.906; p < 0.001) in the investigated population. Cumulative risk of death according to WBCS (ranging from 0 to 3 points) was as follows: 0 points—10.9%, 1 point—23.5%, 2 points—33.1%, 3 points—34.1%. Conclusions: Based on differential blood count, the proposed WBCS is easy to use and can be helpful in predicting mortality among severe COVID-19 patients. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections: 2nd Edition)

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13 pages, 225 KB

Open AccessArticle

Associations Between Nasal Receptors and Olfactory Dysfunction and Dysgeusia in Coronavirus Disease 2019 (COVID-19)

by Ana María Piqueras-Sánchez, José Francisco López-Gil, Diego Hellín-Meseguer, Juan Cabezas-Herrera, Ginés Francisco Blesa-Llaona, José Meseguer-Cabezas, Enrique Bernal-Morell, Alfredo Minguela-Puras and José Antonio Díaz-Manzano

J. Clin. Med. 2026, 15(4), 1659; https://doi.org/10.3390/jcm15041659 - 22 Feb 2026

Cited by 1 | Viewed by 787

Abstract

Background/Objectives: Olfactory dysfunction and dysgeusia are common neurosensory manifestations of Coronavirus Disease 2019 (COVID-19), affecting approximately 60% of patients. These symptoms have been mechanistically linked to receptors involved in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) cell entry, including angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), furin, and neuropilin-1 (NRP1), which are highly expressed in the olfactory epithelium. Nevertheless, clinical evidence supporting a direct association between receptor expression and sensory impairment remains inconsistent. Methods: We conducted a multicenter, observational, cross-sectional study including 104 adults with polymerase chain reaction–confirmed SARS-CoV-2 infection during the first and second pandemic waves. Approximately 75 days after diagnosis, nasal and/or pharyngeal samples were obtained to quantify gene expression levels of ACE2, TMPRSS2, furin, and NRP1 using quantitative polymerase chain reaction. Olfactory dysfunction and dysgeusia were recorded as dichotomous variables. Logistic regression analyses were performed with adjustment for age, sex, and race, considering receptor expression as continuous variables and as tertiles. Missing data were addressed using multiple imputation methods. Results: Olfactory dysfunction was reported by 37.5% of participants, and dysgeusia by 36.5%. No statistically significant associations were observed between baseline expression levels of ACE2, TMPRSS2, furin, or NRP1 and the presence of olfactory dysfunction or dysgeusia in either adjusted continuous or categorical models. Although these associations did not reach statistical significance, higher ACE2 and furin expression showed a nonsignificant trend toward an increased probability of sensory alterations, whereas intermediate NRP1 levels were associated with lower disease severity. Conclusions: COVID-19-related olfactory dysfunction and dysgeusia do not appear to be directly determined by isolated baseline expression of SARS-CoV-2 entry receptors. These findings support a multifactorial and dynamic pathophysiological model involving temporal receptor regulation, inflammatory processes, and host-related factors, highlighting the need for longitudinal and interventional studies. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections: 2nd Edition)

12 pages, 628 KB

Open AccessArticle

Clinical Outcomes Associated with Oral Versus Intravenous Antibiotic Therapy in Emergency Department–Discharged Patients with Community-Acquired Pneumonia

by Mohammed Alrashed, Saleh Alyousef, Bader Alamri, Omar Yousef, Hisham AlJarallah, Abdulmajeed Alshehri, Omar A. Almohammed and Ahmed Aljabri

J. Clin. Med. 2025, 14(22), 8167; https://doi.org/10.3390/jcm14228167 - 18 Nov 2025

Viewed by 1973

Abstract

Background: Community-acquired pneumonia (CAP) remains a leading cause of emergency department (ED) visits, hospitalizations, and mortality worldwide. The choice between oral (PO) and intravenous (IV) antibiotic administration in the ED varies based on patient presentation and provider preference, yet the impact of this choice on clinical outcomes, including revisit rates and ED length of stay (LOS), remains unclear. This study aimed to compare PO versus IV antibiotic therapy in CAP patients discharged from the ED in terms of baseline characteristics, treatment outcomes, and healthcare utilization. Method: This retrospective cohort study was conducted at a tertiary care ED at the Ministry of National Guard Health Affairs in Saudi Arabia. Adult patients diagnosed treated with antibiotic for CAP and discharged from the ED between 2020–2024 were included. Patients were categorized into two groups based on antibiotic administration: POIV. The primary results were ED LOS and 30-day revisit rates. Secondary outcomes included time to first antibiotic administration, fluid administration patterns, and baseline risk factors. Data was extracted from the electronic health record and analyzed using descriptive and inferential statistics. Results: A total of 430 patients were included, with 162 (37.7%) receiving PO antibiotics and 268 (62.3%) receiving IV antibiotics. Baseline characteristics showed higher heart rate, respiratory rate, and temperature in the IV group, suggesting more severe presentations. The mean ED LOS was similar between groups (oral: 6.5 ± 4.9 h vs. IV: 6.4 ± 4.5 h; p = 0.5559). However, the 30-day ED revisit rate was significantly lower in the IV group (23.1%) compared to oral group (34.0%) (p = 0.0146). IV fluids were administered more frequently in the IV group (60.4% vs. 22.2%). Conclusions: While both PO and IV antibiotic strategies resulted in similar ED LOS, IV antibiotic use was associated with a significantly lower 30-day revisit rate. These findings support the need for risk-based treatment decisions in the ED and highlight opportunities for antibiotic stewardship to improve patient outcomes. Full article

(This article belongs to the Special Issue Update on Acute Severe Respiratory Infections: 2nd Edition)

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